Pomalidomide in Combination With Low-dose Dexamethasone or Pomalidomide in Combination With Low-dose Dexamethasone and Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Following Lenalidomide-based Therapy in the First or Second Line Setting

NCT01946477 | Completed Phase 2 Results

• 1 other identifier: CC-4047-MM-014
• Study Type: interventional
• Target: 186
• Locations: 4 countries
• Sites: 49

Brief Summary

This trial will evaluate the efficacy and safety of combination of pomalidomide (POM) and low-dose dexamethasone (LD-Dex) (Cohort A) or the combination of pomalidomide (POM) , daratumumab (DARA) and low-dose dexamethasone (LD-Dex) (Cohort B) in subjects with relapsed or refractory multiple myeloma who have received a first or second line treatment of lenalidomide-based therapy. This trial will test the hypothesis for Cohort A that the proportion of patients will have an Overall Response Rate (ORR) of \> 30 % to reveal that Pomalidomide is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort B that the proportion of patients will have an Overall Response Rate (ORR) of \> 70 % to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort C that the proportion of patients will have an Overall Response Rate (ORR) of \>60% to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide. This treatment will be in only Japanese patients.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma, MM, cancer, oncology, hematology, plasma, neoplasm, plasmacytoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR per Modified International Myeloma Working Group (mIMWG) Criteria is defined as the percentage of participants who achieve best overall response of Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR). CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours PR=≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours

  From first dose until disease progression or end of treatment whichever occurs first (Up to 130 months)

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  From first dose until the first documented disease progression, or death whichever occurs first (Up to 130 months)

• Overall Survival (OS)

  From first dose until death due to any cause (Up to 130 months)

• Duration of Response (DoR)

  From first dose until the first documented disease progression, or death whichever occurs first (Up to 130 months)

• Time to Response (TTR)

  From first dose until the first documented response (Up to 130 months)

• Time to Progression (TTP)

  From first dose until the first documented disease progression whichever occurs first (Up to 130 months)

Study Arms (2)

Pomalidomide + dexamethasone

EXPERIMENTAL

Each subject enrolled in the study will take oral pomalidomide (4 mg) once daily on Days 1-21 and dexamethasone 40 mg/day (\< 75 years old) or 20 mg/day (\>75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.

Drug: Pomalidomide; Drug: Dexamethasone

Pomalidomide + Dexamethasone + Daratumumab

EXPERIMENTAL

Each subject enrolled in the study will take oral pomalidomide (4 mg) once daily on Days 1-21 and dexamethasone 40 mg/day (\< 75 years old) or 20 mg/ day (\>75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle and daratumumab administered intravenously (IV) at a starting dose of 16 mg/kg at following schedule: * Days 1, 8, 15, and 22 of a 28-day cycle for Cycle 1 and Cycle 2 * Days 1 and 15 for Cycle 3 through Cycle 6 * Day 1 for Cycle 7 and each cycle thereafter until disease progression

Drug: Pomalidomide; Drug: Dexamethasone; Drug: Daratumumab

Interventions

Pomalidomide DRUG

Also known as: CC-4047

Pomalidomide + Dexamethasone + Daratumumab; Pomalidomide + dexamethasone

Dexamethasone DRUG

Also known as: dex

Pomalidomide + Dexamethasone + Daratumumab; Pomalidomide + dexamethasone

Daratumumab DRUG

Pomalidomide + Dexamethasone + Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Adults (age ≥ 18 years at the time of signing the ICD) with documented diagnosis of MM and measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours).
• Subjects enrolling in Cohort A (POM+LD-dex) must have received 2 prior treatment lines of anti-myeloma therapy. Subjects enrolling in Cohort B and Cohort C (POM+DARA+LD-dex) must have received 1 or 2 prior treatment lines of anti-myeloma therapy.
• All subjects must have received prior treatment with LEN or a LEN-containing regimen for at least 2 consecutive cycles as the most recent treatment regimen.
• All subjects must have documented disease progression during or after their last antimyeloma therapy.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Subjects must understand and voluntarily sign an ICD prior to any study related assessments/procedures being conducted.
• Subjects must be able to adhere to the study visit schedule and other protocol requirements.
• All subjects must provide an adequate bone marrow sample at screening that definitively evaluates the presence or absence of myelodysplastic changes.
• Females with child-bearing potential (FCBP†) must agree to use 2 reliable forms of contraception\* simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including during dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe. For subjects enrolled in Cohort B and Cohort C, pregnancy prevention and testing will continue until 3 months after last dose of daratumumab.
• Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation. Female subjects enrolled in Cohort B and Cohort C must agree to abstain from breastfeeding and donating eggs during study participation and until 3 months after last dose of daratumumab.
• Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 28 days following discontinuation from this study, even if he has undergone a successful vasectomy. Male subjects enrolled in Cohort B and Cohort C must agree to use a latex condom during any sexual contact with FCBP while participating in the study and until 3 months after last dose of daratumumab.
• Males must also agree to refrain from donating semen or sperm during the treatment phase and for 28 days after discontinuation from this study treatment. Male subjects enrolled in Cohort B and Cohort C must also agree to refrain from donating semen or sperm during the treatment phase and until 3 months after last dose of daratumumab.
• All subjects must agree to refrain from donating blood while on study therapy and for 28 days after discontinuation from this study treatment.
• All subjects must agree not to share medication.

You may not qualify if:

• The presence of any of the following will exclude a subject from study enrollment:
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• Any of the following laboratory abnormalities:
• Absolute neutrophil count \< 1,000/μL
• Platelet count \< 75,000/μL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells; or a platelet count \< 30,000/μL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells.
• Severe renal impairment (Creatinine Clearance \[CrCl\] \< 30 mL/min) requiring dialysis.
• Corrected serum calcium \> 11.5 mg/dL (\> 2.8 mmol/L)
• Hemoglobin \< 8 g/dL (\< 4.9 mmol/L; prior red blood cell transfusion or recombinant human erythropoietin use is permitted)
• Serum SGOT/AST or SGPT/ALT \> 3.0 x the upper limit of normal (ULN)
• Serum total bilirubin \> 2.0 mg/dL (34.2 μmol/L); or \> 3.0 x ULN for subjects with hereditary benign hyperbilirubinemia
• Prior history of malignancies, other than MM, unless the subject has been free of the disease for more than 5 years. Allowed exceptions include the following:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast
• Incidental histological finding of prostate cancer (TNM \[tumor, nodes, metastasis\] stage of T1a or T1b)
• Previous therapy with pomalidomide or daratumumab

Sponsors & Collaborators

• Celgene: lead

Study Sites (49)

Local Institution - 126

Tucson, Arizona, 85724, United States

Location

Local Institution - 137

Greenbrae, California, 94904-2007, United States

Location

Local Institution - 109

Los Angeles, California, 90095-1670, United States

Location

Local Institution - 104

Pleasant Hill, California, 94523, United States

Location

Local Institution - 108

Whittier, California, 90603, United States

Location

Local Institution - 138

Denver, Colorado, 80218, United States

Location

Local Institution - 120

Stamford, Connecticut, 06902, United States

Location

Local Institution - 145

Jacksonville, Florida, 32256, United States

Location

Local Institution - 127

Orlando, Florida, 32804, United States

Location

Local Institution - 133

Pembroke Pines, Florida, 33028, United States

Location

Local Institution - 136

St. Petersburg, Florida, 33705, United States

Location

Local Institution - 134

Fairway, Kansas, 66205, United States

Location

Local Institution - 142

Topeka, Kansas, 66606, United States

Location

Local Institution - 124

Louisville, Kentucky, 40207, United States

Location

Local Institution - 103

Westminster, Maryland, 21157, United States

Location

Local Institution - 146

Gross Pointe, Michigan, 48236, United States

Location

Local Institution - 102

Kansas City, Missouri, 64111, United States

Location

Local Institution - 110

St Louis, Missouri, 63110, United States

Location

Local Institution - 118

East Orange, New Jersey, 07018, United States

Location

Local Institution - 101

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 129

Glens Falls, New York, 12801, United States

Location

Local Institution - 149

The Bronx, New York, 10467, United States

Location

Local Institution - 130

Durham, North Carolina, 27705, United States

Location

Local Institution - 123

Cleveland, Ohio, 44106, United States

Location

Local Institution - 121

Cleveland, Ohio, 44111, United States

Location

Local Institution - 115

Cleveland, Ohio, 44195, United States

Location

Local Institution - 122

Mayfield Heights, Ohio, 44124, United States

Location

Local Institution - 107

Hershey, Pennsylvania, 17033-0850, United States

Location

Local Institution - 135

Chattanooga, Tennessee, 37404, United States

Location

Local Institution - 131

Nashville, Tennessee, 37203, United States

Location

Local Institution - 128

Lubbock, Texas, 79410, United States

Location

Local Institution - 143

Plano, Texas, 75093, United States

Location

Local Institution - 106

Spokane, Washington, 99218, United States

Location

Local Institution - 113

Calgary, Alberta, T2N 2T9, Canada

Location

Local Institution - 144

Surrey, British Columbia, V3V 1Z2, Canada

Location

Local Institution - 114

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 139

Moncton, New Brunswick, E1C 8X3, Canada

Location

Local Institution - 140

St. John's, Newfoundland and Labrador, A1B3V6, Canada

Location

Local Institution - 112

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 148

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 117

Montreal, Quebec, H3A 1A1, Canada

Location

Local Institution - 205

Fukuoka, Fukuoka, 810-8563, Japan

Location

Local Institution - 208

Kamogawa, 296-8602, Japan

Location

Local Institution - 204

Kyoto, 602-8566, Japan

Location

Local Institution - 202

Nagoya, 467-8602, Japan

Location

Local Institution - 203

Okayama, 701-1192, Japan

Location

Local Institution - 206

Shibukawa-shi, Gunma-ken, 377-0280, Japan

Location

Local Institution - 207

Toyohashi, 441-8570, Japan

Location

Local Institution - 119

San Juan, 00927, Puerto Rico

Location

Related Publications (4)

• Pelligra CG, Parikh K, Guo S, Chandler C, Mouro J, Abouzaid S, Ailawadhi S. Cost-effectiveness of Pomalidomide, Carfilzomib, and Daratumumab for the Treatment of Patients with Heavily Pretreated Relapsed-refractory Multiple Myeloma in the United States. Clin Ther. 2017 Oct;39(10):1986-2005.e5. doi: 10.1016/j.clinthera.2017.08.010. Epub 2017 Sep 28.

  PMID: 28967482 BACKGROUND

• Bahlis NJ, Siegel DS, Schiller GJ, Samaras C, Sebag M, Berdeja J, Ganguly S, Matous J, Song K, Seet CS, Acosta-Rivera M, Bar M, Quick D, Anz B, Fonseca G, Chung W, Lee K, Mouro J, Agarwal A, Reece D. Pomalidomide, dexamethasone, and daratumumab immediately after lenalidomide-based treatment in patients with multiple myeloma: updated efficacy, safety, and health-related quality of life results from the phase 2 MM-014 trial. Leuk Lymphoma. 2022 Jun;63(6):1407-1417. doi: 10.1080/10428194.2022.2030477. Epub 2022 Feb 8.

  PMID: 35133221 DERIVED

• Pierceall WE, Amatangelo MD, Bahlis NJ, Siegel DS, Rahman A, Van Oekelen O, Neri P, Young M, Chung W, Serbina N, Parekh S, Agarwal A, Thakurta A. Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma. Clin Cancer Res. 2020 Nov 15;26(22):5895-5902. doi: 10.1158/1078-0432.CCR-20-1781. Epub 2020 Sep 14.

  PMID: 32928795 DERIVED

• Siegel DS, Schiller GJ, Song KW, Agajanian R, Stockerl-Goldstein K, Kaya H, Sebag M, Samaras C, Malek E, Talamo G, Seet CS, Mouro J, Pierceall WE, Zafar F, Chung W, Srinivasan S, Agarwal A, Bahlis NJ. Pomalidomide plus low-dose dexamethasone in relapsed refractory multiple myeloma after lenalidomide treatment failure. Br J Haematol. 2020 Feb;188(4):501-510. doi: 10.1111/bjh.16213. Epub 2019 Oct 6.

  PMID: 31588567 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Plasmacytoma

Interventions

pomalidomide; Dexamethasone; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2013
• First Posted: September 19, 2013
• Study Start: May 29, 2014
• Primary Completion: April 30, 2025
• Study Completion: May 26, 2025
• Last Updated: May 22, 2026
• Results First Posted: May 22, 2026

Record last verified: 2026-04

Locations

US (33); PR (1); JP (7); CA (8)